Regulation of the Th1 genomic locus from Ifng through Tmevpg1 by T-bet.

Collier SP, Henderson MA, Tossberg JT, Aune TM
J Immunol. 2014 193 (8): 3959-65

PMID: 25225667 · PMCID: PMC4185266 · DOI:10.4049/jimmunol.1401099

Long noncoding RNAs (lncRNAs), critical regulators of protein-coding genes, are likely to be coexpressed with neighboring protein-coding genes in the genome. How the genome integrates signals to achieve coexpression of lncRNA genes and neighboring protein-coding genes is not well understood. The lncRNA Tmevpg1 (NeST, Ifng-AS1) is critical for Th1-lineage-specific expression of Ifng and is coexpressed with Ifng. In this study, we show that T-bet guides epigenetic remodeling of Tmevpg1 proximal and distal enhancers, leading to recruitment of stimulus-inducible transcription factors, NF-κB and Ets-1, to the locus. Activities of Tmevpg1-specific enhancers and Tmevpg1 transcription are dependent upon NF-κB. Thus, we propose that T-bet stimulates epigenetic remodeling of Tmevpg1-specific enhancers and Ifng-specific enhancers to achieve Th1-lineage-specific expression of Ifng.

Copyright © 2014 by The American Association of Immunologists, Inc.

MeSH Terms (14)

Animals Cell Lineage Enhancer Elements, Genetic Epigenesis, Genetic Genetic Loci Interferon-gamma Mice Mice, Inbred BALB C Proto-Oncogene Protein c-ets-1 Regulatory Sequences, Nucleic Acid RNA, Long Noncoding T-Box Domain Proteins Th1 Cells Transcription Factor RelA

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